Nephron最新文献

Background: Mitochondria are central regulators of cellular metabolism, redox signaling, and apoptosis. Their dysfunction plays a pivotal role in the pathogenesis of kidney diseases, including acute kidney injury and diabetic nephropathy.

Summary: Recent advances have unveiled horizontal mitochondrial transfer as a novel intercellular communication by which renal cells exchange mitochondria to promote tissue repair through the modulation of metabolic processes, oxidative stress, apoptosis, and fibrosis.

Key findings: Horizontal mitochondrial transfer, mediated by tunneling nanotubes and extracellular vesicles, has emerged as a potential homotypic rescue mechanism between injured tubular and glomerular cells. In addition, heterotypic mitochondrial transfer from mesenchymal stromal cells to renal cells has been described. These findings open new perspectives for exploring therapeutic mitochondrial transplantation in both acute and chronic kidney diseases. Nonetheless, significant challenges remain, including elucidating the poorly characterized biological mechanisms underlying mitochondrial transfer, optimizing delivery strategies, and defining the long-term safety and efficacy of mitochondrial-based therapies.

Introduction: Coenzyme Q8B (COQ8B) nephropathy is an autosomal recessive hereditary disorder caused by primary coenzyme Q10 (CoQ10) deficiency. It manifests as a genetic steroid-resistant nephrotic syndrome (SRNS), typically of childhood-onset. CoQ10 supplementation is a treatment option; however, it is not always effective in an entire patient population, leading to end-stage kidney disease. Kidney transplantation (KTx) is an effective treatment option for genetic SRNS; however, living KTx within biologically related members is associated with increased risk of allograft failure in recipients and future kidney dysfunction in donors. Here, we present two successful cases of living kidney donations from heterozygous carrier parents to their siblings with COQ8B nephropathy.

Case presentation: The family comprised two parents and three siblings. Two of the daughters were diagnosed with proteinuria at 11 and 8 years of age, respectively. COQ8B nephropathy diagnosis was confirmed by next-generation and Sanger sequencing analysis, which revealed a novel compound heterozygous mutation in the COQ8B gene (c.737G>A and c.1468C>T). An older sister missed an opportunity for CoQ10 supplementation due to late diagnosis, whereas a younger sister did not respond to CoQ10 supplementation. Living kidney donation from father to the older sister and from mother to the younger sister was successfully performed without posttransplant recurrence in recipients or kidney dysfunction in donors within 5 and 2 years of follow-up.

Conclusion: Parent-to-child KTx may be an effective treatment option within family members affected with COQ8B nephropathy.

Acute kidney injury (AKI) pathophysiology and repair are heterogenous processes, and clinical outcomes are difficult to predict. As a result, promising treatments in preclinical models have failed to translate to human subjects, and treatment options for AKI are primarily supportive. To address this, one of the AKI & CRRT 2025 pre-conference symposium plenary sessions showcased cutting edge translational work to guide the scientific community of AKI investigators. Topics included those focused on stratifying risk for AKI reflected in the concept of kidney fitness, characterizing the molecular phenotypes of AKI, improving diagnostics, and identifying novel therapeutic targets. This article provides a review of these topics and a summary of how they address challenges to translating new therapies in AKI from bench to bedside.

Introduction: Left ventricular hypertrophy (LVH) is a common cardiovascular complication in chronic kidney disease (CKD), driven by anemia and nutritional deficiencies. The hemoglobin-to-red cell distribution width ratio (HRR) reflects these factors, but its association with LVH in CKD remains unclear. This study aimed to investigate the relationship between HRR and LVH in non-dialysis CKD stage 3-5 patients.

Methods: In this cross-sectional study, 195 patients were included. HRR was calculated from hemoglobin and red cell distribution width. LVH was diagnosed by echocardiography (LV mass index >115 g/m² men, >95 g/m² women). Logistic regression assessed HRR-LVH association, including subgroup and restricted cubic spline analyses. Mediation analysis explored the role of intact parathyroid hormone (iPTH) and N-terminal pro-brain natriuretic peptide (NT-proBNP).

Results: Patients with LVH (n=40) had significantly lower HRR (median 0.62 vs. 0.81, P<0.001). HRR was inversely associated with LVH (adjusted OR 0.41 per SD increase, P=0.005), with the highest HRR tertile showing the lowest LVH risk (adjusted OR 0.23, P=0.044). Subgroup analyses showed consistent associations. Mediation analysis indicated iPTH and NT-proBNP explained 37% and 21.1% of the HRR-LVH relationship.

Conclusion: HRR may be a simple marker for cardiovascular risk stratification in CKD. Prospective studies should assess whether interventions targeting HRR reduce LVH incidence.

Background: Kidney transplantation and dialysis are the two main modalities of kidney replacement therapy, and both are increasingly challenged by the current climate emergency landscape. Dialysis has long been scrutinised for its high energy and water demands, but transplantation, whilst generally more sustainable over the long term, also warrants critical evaluation concerning environmental accountability, equity, and resilience.

Summary: In this review, we compare the environmental and structural dimensions of dialysis and transplantation, while examining how climate change uniquely affects transplant recipients and grafts. We highlight the vulnerabilities of immunosuppressed recipients to heat stress and infectious diseases, the risks of cold-chain disruption for organ preservation and shipment, and the impact of graft failure necessitating return to dialysis. We then consider how green nephrology principles can be applied to transplantation, drawing on emerging UK data, global policy frameworks such as the European Green Deal, and lessons from low- and middle-income countries (LMICs). Digital healthcare solutions such as hybrid virtual clinics are explored as tangible strategies to reduce the carbon footprint of follow-up care. Recent life-cycle analyses also provide comparative estimates of dialysis and transplantation emissions, underscoring the importance of nuanced evaluation of both modalities.

Key messages: We conclude with a forward-looking agenda for clinicians and policymakers to embed environmental and social responsibility into both dialysis and transplantation, ensuring that kidney replacement therapy as a whole is resilient and sustainable in a warming world.

Background: Acute kidney injury (AKI) represents a multifaceted clinical syndrome marked by precipitous loss of kidney function, high morbidity and mortality, and a strong propensity for progression to chronic kidney disease. Collectively, these challenges underscore the imperative to delineate conserved molecular and signaling networks that are uniformly engaged across diverse AKI etiologies.

Summary: Herein, we survey five emerging research domains poised to transform AKI pathophysiology and therapeutic paradigms. First, lymphatic network remodeling has been implicated as a critical determinant of renal immunodynamics and interstitial fluid homeostasis, whereby modulation of VEGF-C/D signaling reshapes immune cell trafficking and fibrogenic responses. Second, we will cover emerging evidence that positions macrophage ferritin heavy chain as a key regulator of macrophage phenotype and subsequent kidney ferroptosis susceptibility via coordinated regulation of synuclein-⍺, and Spic. Third, we will emphasize incorporating development as a biological variable into experimental design based on evidence that identifies age-dependent divergences in injury susceptibility, and progression of disease. Fourth, we cover mechanosensitive ion channels that are activated by therapeutic ultrasound offering novel opportunities to harness the cholinergic anti-inflammatory pathway for nephroprotection. Finally, targeting tubular epithelial cell senescence and mitochondrial bioenergetics as a promising approach to limit progression of kidney disease will be discussed.

Key messages: Collectively, these emerging mechanisms deepen our understanding of AKI pathophysiology and unveil novel therapeutic targets with the potential to transform the treatment landscape.

Introduction: Nephronophthisis (NPHP) is an autosomal recessive kidney disease resulting mainly from primary cilium defects, with unspecific and variable symptoms that can progress to kidney failure needing replacement therapy at a young age. Currently, up to 64% of likely NPHP cases can be diagnosed by assessing known genes. Therefore, there is a need to gain more insight in what genes can cause this disease.

Methods: In a diagnostic setting, we performed broad genetic testing in patients with advanced kidney disease. We carried out in silico and in vitro analyses for TMEM72, including immunohistochemistry and affinity proteomics, and in vivo experiments to further interpret our findings.

Results: We identified biallelic TMEM72 variants in nine patients from six families with a phenotype suggestive for NPHP. Five families presented with kidney failure at a (young) adult age. One family had a different phenotype with prenatal onset of kidney failure and neurological symptoms. The phenotypes of the patients correspond to TMEM72 expression mainly in the kidney. In silico analyses indicate that homozygous loss-of-function variants are likely not tolerated in TMEM72. Immunohistochemistry staining of kidney biopsies revealed altered localization and expression of TMEM72 in cases compared to controls. In human-derived tubuloids, we showed that TMEM72 localizes to the cilium. Furthermore, using an affinity proteomics approach, we found an association of TMEM72 and ciliary function, more specifically in selective ciliary cholesterol transport.

Conclusion: We present the first genetic evidence, underlined by immunohistochemistry and protein binding assays, linking TMEM72 variants to kidney disease and ciliary function. We conclude that TMEM72 is a candidate gene for NPHP. Future work is needed to further characterize TMEM72 variants and unravel its disease mechanism.

Introduction: In patients with chronic kidney disease (CKD) of diverse causes, obesity and metabolic syndrome (MS) accelerate disease progression. Therapeutic exercise could be effective in treating obesity and MS in patients with CKD. However, the evidence in this area is limited. The aim of this research is to evaluate the effect of an individualized exercise program on major metabolic and renal outcomes in patients with CKD, obesity and MS.

Methods: This was an interventional exploratory study that included patients with established CKD - estimated glomerular filtration rate (eGFR) ≥ 30 ml/min, obesity and MS treated by therapeutic exercise (aerobic and resistance) for 6 months. We evaluated changes in renal outcomes - measured glomerular filtration rate (mGFR) with iohexol-DBS and albuminuria, and metabolic outcomes - weight and MS trait. Biochemical, anthropometric and renal function were performed every 3 months.

Results: Forty patients were evaluated. All were overweight or obese, mGFR was 58 ± 20 ml/min and urine albumin-creatinine ratio (UACR) 256 mg/g [IQR: 38-774]. Based on weight reduction (>5%), patients were classified as "responders" (n=30) and "non-responders" (n=10). Responders had a major reduction in body mass index (BMI) from 35 ± 4 to 31 ± 4 Kg/m² (p<0.001), triglycerides, HbA1c, systolic and diastolic blood pressure and UACR from 222 [20 - 610] to 89 [17 - 413] mg/g (p<0.01), whereas mGFR diminished (≥7%) in half of them and remained stable in the other half. Non-responders experienced no changes. No major side effects were observed.

Conclusion: In patients with CKD, obesity and MS, exercise is an effective treatment to reduce weight, MS traits and albuminuria. Changes in mGFR are heterogeneous. Understanding the impact of weight reduction on glomerular filtration rate (GFR) changes is crucial in CKD. The role of exercise in Nephrological Care deserves further attention. The study trial registration number is NCT06576518.